Arginine

Placebo-controlled studies

In a randomized, double-blind, placebo-controlled study, 153 patients were randomly assigned after a first ST-segment elevation myocardial infarction to l -arginine or matching placebo for 6 months [ ]. The dosage of arginine was 1 g tds for 1 week, 2 g tds in week 2, and 3 g tds in subsequent weeks for 6 months. Six (8.6%) of those who took l -arginine died during the 6-month study period compared with none in the placebo group. Because of concerns about safety, the data and safety monitoring committee closed enrolment to the study. The authors proposed several possible mechanisms. The proposed beneficial mechanism of arginine is increased nitric oxide synthesis by vascular endothelium, since arginine is a substrate for the endothelial-specific isoform of nitric oxide synthase (eNOS). However, if there is deficiency of tetrahydrobiopterin, a co-factor for nitric oxide synthase, instead of generating nitric oxide eNOS becomes a source of reactive oxygen species, and this could be enhanced by arginine. Arginine supplementation also increases homocysteine production, which can result in worsening of endothelial function and atherosclerosis. Furthermore, if there is atherosclerosis, the inducible isoform of nitric oxide synthase (iNOS) is expressed, resulting in the production of peroxynitrite and consumption of nitric oxide, potentially worsening atherosclerosis. All arginine products are now required to carry a warning on their label about the risk of using them after myocardial infarction. Health Canada has advised that for patients who have not had a previous heart attack, taking arginine is unlikely to present a risk and may provide benefits by helping the body repair damaged vessels in the heart.